Modulation of human mesenchymal stem cell function in a three-dimensional matrix promotes attenuation of adverse remodelling after myocardial infarction

David L. Simpson, Samuel C. Dudley

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The application of tissue engineering (TE) practices for cell delivery offers a unique approach to cellular cardiomyoplasty. We hypothesized that human mesenchymal stem cells (hMSCs) applied to the heart in a collagen matrix would outperform the same cells grown in a monolayer and directly injected for cardiac cell replacement after myocardial infarction in a rat model. When hMSC patches were transplanted to infarcted hearts, several measures for left ventricle (LV) remodelling and function were improved, including fractional area change, wall thickness, -dP/dt and LV end-diastolic pressure. Neovessel formation throughout the LV infarct wall after hMSC patch treatment increased by 37% when compared to direct injection of hMSCs. This observation was correlated with increased secretion of angiogenic factors, with accompanying evidence that these factors enhanced vessel formation (30% increase) and endothelial cell growth (48% increase) in vitro. These observations may explain the in vivo observations of increased vessel formation and improved cardiac function with patch-mediated cell delivery. Although culture of hMSC in collagen patches enhanced angiogenic responses, there was no effect on cell potency or viability. Therefore, hMSCs delivered as a cardiac patch showed benefits above those derived from monolayers and directly injected. hMSCs cultured and delivered within TE constructs may represent a good option to maximize the effects of cellular cardiomyoplasty.

Original languageEnglish (US)
Pages (from-to)192-202
Number of pages11
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume7
Issue number3
DOIs
StatePublished - Mar 1 2013

Keywords

  • Cell therapy
  • Mesenchymal stem cells
  • Myocardial infarction
  • Neovascularization
  • Paracrine effect
  • Tissue engineering

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